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Repotrectinib (TPX-0005) ALK inhibitor

Name: Repotrectinib (TPX-0005)
Brand: Selleck Chemicals
SKU: S8583
Availability: InStock
Rating: 5 (12 reviews)

Cat.No.S8583

Repotrectinib (TPX-0005) is a novel ALK/ROS1/TRK inhibitor with the IC50 values of 1.01 nM for WT ALK, 1.26 nM for ALK(G1202R), and 1.08 nM for ALK(L1196M); it is also a potent SRC inhibitor (IC50 5.3 nM).

Chemical Structure

Molecular Weight: 355.37

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.97%

99.97

Related Targets	EGFR VEGFR PDGFR FGFR c-Met Src FLT3 HER2 c-Kit Bcr-Abl MEK BTK IGF-1R Trk receptor Syk Axl CSF-1R c-RET FAK Mertk Tie-2 DYRK Tyro3 Ephrin receptor ROS1 Pyk2 RON DDR ACK Fer kinase
Related Products	TAE684 (NVP-TAE684) GSK1838705A AZD3463 AP26113-analog (ALK-IN-1) Ensartinib dihydrochloride ASP3026

Chemical Information, Storage & Stability

Molecular Weight	355.37	Formula	C₁₈H₁₈FN₅O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1802220-02-5	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1CNC(=O)C2=C3N=C(C=CN3N=C2)NC(C4=C(O1)C=CC(=C4)F)C

Solubility

In vitro
Batch:

DMSO : 37.5 mg/mL ( (105.52 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 7 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.880mg/ml (5.29mM)	Taking the 1 mL working solution as an example, add 50 μL of 37.5 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to make it clear. Volume up to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	ROS1 ^[2] Trk receptor ^[2] WT ALK ^[1] (Cell-free assay) 1.01 nM ALK(L1196M) ^[1] (Cell-free assay) 1.08 nM ALK(G1202R) ^[1] (Cell-free assay) 1.26 nM Src ^[1] (Cell-free assay) 5.3 nM
In vitro	Repotrectinib (TPX-0005) is an orally available and potent ATP-competitive inhibitor against ALK, ROS1, TRKA, TRKB and TRKC recombinant kinases and their corresponding clinical resistant mutants. It demonstrates potent anti-proliferative activity in the range of sub-nanomolar to low nanomolar in a number of human cancer cell lines and engineered stable cell lines expressing the targeted oncogenes or their solvent front mutants, accompanied by inhibition of target phosphorylation and concomitant inactivation of downstream effectors such as ERK, AKT and STAT3^[2]. This compound inhibits H2228 cell migration in a wound healing assay with similar activity to saracatinib. It is able to not only inhibit the wild-type and a broad spectrum of mutant ALKs, but also overcome primary resistance and suppress metastatic features by inhibiting SRC^[1].
In vivo	In patient derived xenograft tumor models, TPX-0005 treatment results in significant regression of tumors harboring the oncogenic ALK, ROS1 and TRKC fusions. Moreover, in a series of mouse xenograft tumor models, TPX-0005 exhibits marked anti-tumor activity not only in tumors harboring the wildtype oncogenic targets but also in tumors harboring the oncogenes with the solvent front mutations via inhibition of the target phosphorylation^[2].
References	http://cancerres.aacrjournals.org/content/76/14_Supplement/2132 http://cancerres.aacrjournals.org/content/77/13_Supplement/3168

Applications

Methods	Biomarkers	Images	PMID
Western blot	pEGFR / pERK / pAKT / pSTAT3 / pPaxillin / Pyap1 / cleaved caspase-3		29433983
Immunofluorescence	pSTAT3(Y705) / STAT3		29433983

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03093116	Recruiting	Locally Advanced Solid Tumors\|Metastatic Solid Tumors	Turning Point Therapeutics Inc.\|Zai Lab (Shanghai) Co. Ltd.	March 7 2017	Phase 1\|Phase 2

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